The effects of developmental and current niches on oligodendrocyte precursor dynamics and fate

Abstract

Oligodendrocyte precursor cells (OPCs), whose primary function is to generate myelinating oligodendrocytes, are distributed widely throughout the developing and mature central nervous system. They originate from several defined subdomains in the embryonic germinal zones at different developmental stages and in the adult. While many phenotypic differences have been observed among OPCs in different anatomical regions and among those arising from different germinal zones, we know relatively little about the molecular and cellular mechanisms by which the historical and current niches shape the behavior of oligodendrocyte lineage cells. This minireview will discuss how the behavior of oligodendrocyte lineage cells is influenced by the developmental niches from which subpopulations of OPCs emerge, by the current niches surrounding OPCs in different regions, and in pathological states that cause deviations from the normal density of oligodendrocyte lineage cells and myelin.

Keywords: Astrocyte; Development; Myelin; NG2; Niche; Oligodendrocyte precursor; PDGF; Proliferation.

Figure 1.

Schematics showing the effects of various niches on OPC and OL dynamics A. Influence of developmental niches A1. OPCs in the posterior (caudal) regions (blue) exhibit greater proliferative response to PDGF compared to those in the anterior (rostral) regions of the brain (pink), partly due to the chemokine GRO-α (CXCL1) secreted by astrocytes. Gray curved arrows denote greater proliferation. A2. OPCs arising from the dorsal germinal zones (green) appear to be endowed with greater proliferative abilities, both in the brain and spinal cord, than those from ventral origin (brown). A3. OPCs from the dorsal germinal zones remain primarily in the OL lineage, whereas, some OPCs in the prenatal ventral forebrain, presumably of ventral origin, differentiate into protoplasmic astrocytes. B. Influence of the current neuroanatomical niches – the gray and white matter OPCs in the white matter (corpus callosum) appear more elongated, proliferate more extensively (gray curved arrows), and differentiate into OLs more rapidly than those in the gray matter (neocortex). Insets indicate NG2 immunolabeling showing differences in density and morphology of OPCs in the gray and white matter. C. Influence of the niches created in pathological states of OLs and myelin C1. Under normal state, the density of OPCs and OLs is tightly regulated. C2. When there is loss of mature OLs or myelin, OPCs proliferate (gray curved arrows) and restore the original OL/myelin density. Hollow arrows indicate possible signaling from dead cells to microglia (pink, MG), and possible subsequent signaling from activated microglia to OPCs. Cells with dotted lines indicate dying cells. C3. When there is loss of OPCs, remaining OPCs proliferate to maintain original density. C4. Conversely, when excess OLs are generated, they do not survive, and normal OL/myelin density is restored.